Transcript Medicine Case Presentation

To Inhale or Not to Inhale?
Sukhjinder Sidhu
Interior Health Pharmacy Resident
September 13, 2013
Learning Objectives
• Describe the pathophysiology of COPD
• Become familiar with the clinical presentation
and how to access severity of COPD
• Be able to explain the evidence for treatment
of mild COPD
• Describe the role of ICS, LABA in management
of COPD
Our Patient
ID
65 y.o. male (72.6 kg; 170 cm). Admitted Aug 21, 2013 to CTU.
CC/HPI
SOB x 5-6 days accompanied by chest pain
Some nausea and generalized weakness x 1/52
Allergies
NKDA
Social Hx
Quit smoking 28 years ago (75 pack/yr hx)
Ø Alcohol or illicit drug use
Assisted living; wife died 3 months ago
Our Patient
PMHx:
MPTA:
C. Difficile
Metronidazole 500 mg PO TID x 14 days (finished Aug 18, 2013)
Essential
thrombocythemia
Hydroxyurea 1000 mg PO daily
Schizo-affective
Risperidone 1 mg PO BID
Anxiety
Diazepam 10 mg PO QID PRN
Citalopram 40 mg PO daily
HTN
None
Hypothyroidism
Levothyroxine 75 mcg PO daily
Chronic prostatitis Ciprofloxacin 1000 mg PO daily
COPD
None
Esophagitis/PUD
Rabeprazole 20 mg PO BID
Tums 10 tab PO daily
Nausea
Dimenhydrinate 100-200 mg PO BID-TID
Review of Systems
Vitals
T 36.6
HR 113
CNS/Neuro
A&O x 3
HEENT
Ø
RESP
Labored breathing; left side wheezing; Ø cough
CVS
Regular; S1/S2 normal; ECG flipped T’s
GI
6 loose BM today; distended; normal sounds
GU
> 300 mL urine PRV; SrCr 113; eGFR 56
ENDO
TSH 7.31
MSK/Derm
Pale skin
LYTES
Na 124
HEME
Hgb 120 MCV 93.9 WBC 16.5 Neuts 13.53 Plts 1173
K 4.9
Cl 91
BP 105/69
RR 70
O2 sat 92% after neb
Bicarb 22
Investigations
Diagnostics
Day 0
(Admission)
CXR
Hyperinflation consistent with COPD
Day 1
Chest CT
Bilateral pulmonary emboli
CXR
Comparison - Ø HF
V/Q Scan
Bilateral PE
TEE
Moderate pulmonary hypertension
CXR
Tiny bilateral pleural effusions
Day 2
Day 3
Microbiology
Day 1
Stool
C. Difficile Toxin B
Urine
No growth
Course in Hospital
• Assessed by respirology
– Diagnosed with pulmonary emboli
– Diagnosed with COPD
Current Problems & Medications
Indication
Medication
Pulmonary emboli
Nadroparin 13,300 unit SC daily
Warfarin to target INR 2-3
C. Difficile
Vancomycin 125 mg PO Q6H x 7 days
COPD
Fluticasone 500 mcg INH Q12H
Ipratropium 40 mcg INH QID
Salbutamol 200 mcg INH QID & Q1H PRN
Essential
thrombocythemia
Hydroxyurea 500 mg PO TID
Nausea
Dimenhydrinate 50 mg IV Q6H PRN
PUD/Esophagitis
Ranitidine 150 mg PO BID
Schizo-affective
Risperidone 1 mg PO BID
Anxiety
Diazepam 5-10 mg PO QID PRN
Citalopram 40 mg PO daily
Hypothyroidism
Levothyroxine 75 mcg PO daily
DRPs
1. GB is at risk of experiencing subsequent VTE’s or death
secondary to non-adherence to his warfarin therapy and would
benefit from reassessment of therapy.
2. GB is at risk of C. difficile treatment failure secondary to
receiving a short duration of vancomycin therapy and would
benefit from a 10 day duration.
3. GB is at risk of experiencing adverse events secondary to
receiving COPD therapy without a clear diagnosis and unclear
severity and would benefit from reassessment of his COPD
therapy.
4. GB is at risk of developing pneumonia secondary to not
receiving his pneumococcal vaccine and would benefit from a
one-time administration of the vaccine.
DRP Focus
• GB is at risk of experiencing adverse events
secondary to receiving COPD therapy without
a clear diagnosis and unclear severity and
would benefit from reassessment of his COPD
therapy.
COPD
• Gradual & progressive loss of
lung function due to chronic
inflammatory changes
• Chronic airflow limitation
– alveoli lose elasticity
– alveolar destruction
– ↑ mucus production
• Airway closure on expiration,
leading to air trapping &
hyperinflation
nhlbi.nih.gov/health/health-topics/topics/copd/
COPD
• Risk Factors
– Cigarette smoking
– Air pollution
– Exposure to occupational
dusts & chemicals
• Clinical Presentation
–
–
–
–
–
–
Chronic cough
Sputum production
Dyspnea
↑RR
Breathing with pursued lips
Hyperinflation of the lungs
Can Respir J 2008;15(Suppl A):1A-8A
COPD
• Our patient
– COPD stage = mild
•
•
•
•
•
•
•
Hyperinflation present
Ø PFTs
Ø SOB
Ø exacerbations
Ø chronic cough
Ø sputum production
PTA Ø puffers
Goals of Therapy
•
•
•
•
•
Reduce mortality
Prevent or reduce hospitalizations
Reduce frequency & severity of exacerbations
Prevent disease progression
Improve QOL by reducing impairment &
disability
• Reduce adverse events
Therapeutic Approach
Can Respir J 2008;15(Suppl A):1A-8A
Clinical Question
• In a patient with at most mild COPD will an
inhaled corticosteroid with an anticholinergic
compared to a prn short-acting beta agonist
reduce mortality and exacerbations, and
improve quality of life and symptoms without
increasing the risk of adverse events?
Literature Search
Databases
Medline, PubMed
Search Terms
Pulmonary Disease, Chronic Obstructive
Anti-inflammatory Agents
Bronchodilator Agents/ or albuterol/ or ipratropium/
Adrenergic beta-Agonists
Results
8 RCT’s
• TRISTAN
• TORCH
1 Meta-analysis
1 NICE Guideline
TRISTAN
Design
Randomized, double-blind, parallel-group, placebo-controlled
Population
Inclusion:
Diagnosis of mod-severe COPD
Poor reversibility of airflow obstruction
Smoking hx of > 10 pack-years
> 1 episode of acute COPD sx exacerbation/year in previous 3 yrs
with > 1 being in year before trial requiring PO CCS, abx or both
Baseline:
N 1465; mean age 63; ~70-75% male; ~50% current smoker;
FEV1 ~45%; median use of relief meds/day ~3
Intervention
Salmeterol 50 mcg INH BID vs. fluticasone 500 mcg INH BID vs.
salmeterol 50 mcg INH/fluticasone 500 mcg INH BID vs. placebo x 12
months
Primary
Outcome
Improvement in pretreatment FEV1
Lancet 2003; 361:449-56.
TRISTAN
Placebo
Salmeterol
Fluticasone
Combination
FEV1
1264 mL+
1323 mL*+
1302 mL*+
1396 mL*
Exacerbations
1.3/yr
1.04/yr*
1.05/yr*
0.97/yr*
SGRQ
46.3
(47.1)
45.2
(48.7)
45.5+
(49.8)
44.1*
(47.1)
Any treatment-related
adverse event
14%
12%
19%
16%
Cough, breathing
disorder or lower
respiratory infection
2%
2%
2%
<1%
* SS vs. placebo
+ SS vs. combination
Lancet 2003; 361:449-56.
TRISTAN
• Limitations
– Methodological
• How many pts taking anticholinergics?
• No adherence verification
– Clinical
• Primary outcome (FEV1) was a surrogate marker
• Improvement in SGRQ not clinically significant
• High drop-out rates
– Pt has no subjective/objective data for having
moderate-severe COPD
• Pt would not fit criteria to be enrolled in study
Lancet 2003; 361:449-56.
TORCH
Design
Randomized, double-blind, parallel-group, placebo-controlled
Population
Inclusion:
40-80 y.o.
Diagnosis of moderate COPD
Poor reversibility of airflow obstruction
Current/ex-smokers with > 10-pack year hx
Baseline:
N 6112; mean age ~65; 76% male; ~43% current smoker;
FEV1 ~44%; 20% on ICS, 9% on LABA, 27% on combo
Intervention
Salmeterol 50 mcg/fluticasone propionate 500 mcg BID vs.
salmeterol 50 mcg BID vs. fluticasone 500 mcg BID vs. placebo x 3
years
Primary
Outcome
All cause mortality at 3 years
N Engl J Med 2007; 356:775-89.
TORCH
Placebo
Salmeterol
Fluticasone
Combination
Death at 3 yr
15.2%
13.5%
16.0%+
12.6%
Mod-severe
exacerbations
1.13/yr
0.97/yr*+
0.93/yr*+
0.85/yr*
SGRQ
+0.2
-0.8+
-1.8*+
-3.0*
Any adverse event
90
90
90
89
Pneumonia
0.04/yr
12.3%
0.04/yr
13.3%
0.07/yr*
18.3%
0.07/yr*
19.6%
* SS vs. placebo
+ SS vs. combination
N Engl J Med 2007; 356:775-89.
TORCH
• Limitations
– Methodology
• Sponsor employee performed statistical analysis
• Underpowered for mortality outcome
– Clinical
• High drop out rates
• Exacerbations: benefit from fluticasone or combo, must have 5 or
4 exacerbations/yr, respectively – not clinically significant
• Improvement in SGRQ not clinically significant
– Pt has no subjective/objective data for having moderatesevere COPD
• Pt would not fit criteria to be enrolled in study
N Engl J Med 2007; 356:775-89.
Summary of Evidence
Outcomes
TRISTAN
TORCH
Reduce risk of mortality
Ø
Combo: NSS
Fluticasone: NSS
Reduce exacerbations
Combo: SS
Fluticasone: SS
Combo: SS
Fluticasone: SS
Improve QOL
Combo: SS
Fluticasone: NSS
Combo: SS
Fluticasone: SS
Adverse event
Any adverse event ↑ with
combo & fluticasone
↑ pneumonia with combo &
fluticasone
Alternatives for Symptom
Management
• Short-acting beta agonist
– Salbutamol
• Anticholinergics
– Ipratropium
– Tiotropium
• Long-acting beta-agonist
– Salmeterol
– Formeterol
• Inhaled corticosteroids
Application to GB
Salbutamol PRN
Necessary
Ipratropium SCH +
Salbutamol PRN
Fluticasone SCH
Mild COPD?
Ø
Ø
Effective
Yes
Yes
Ø
Safe
Yes
Yes
Ø
Adherence
PRN
At risk
At risk
Ø
↑ med burden
↑ med burden
Patient factors
Cost
Covered through PC Covered through PC Covered through PC
Therapeutic Plan
1.
2.
3.
4.
5.
Discontinue fluticasone 500 mcg INH BID
Discontinue ipratropium 40 mcg INH QID
Discontinue salbutamol 200 mcg INH Q1H PRN
Initiate salbutamol 200 mcg INH Q4H PRN
Recommended one-time pneumococcal
vaccine when stabilized
Monitoring Plan
Efficacy
Degree of Change
When
S:
SOB
Acute exacerbations
Re-admissions
Impairment of daily activities
Absence
Absence
Absence
Minimal – none
Daily/ongoing
Ongoing
Ongoing
Ongoing
O:
Vitals – RR, O2 sat
Remain stable
Daily
Toxicity
Degree of Change
When
S:
Anxiety
Tremor
Nervousness
Palpitations
Presence
Presence
Presence
Presence
First week of tx
First week of tx
First week of tx
First week of tx
O:
Tachycardia
Presence
First week of tx
Follow Up
• All COPD inhaler recommendations were
accepted by MTU team
• Vancomycin increased to 10 days duration
• Applied for SA for rivaroxaban for treatment of
PE
• Counseled patient on warfarin
• Counseled patient on proper inhaler use
• Recommended PFTs once stabilized